Quantification of Calcyclin and Heat Shock Protein 90 in Sera from Women with and without Preeclampsia by Mass Spectrometry

Purpose: The objective of present study is to determine serum levels and placental distribution of two interacting proteins calcyclin and heat shock protein 90 in preeclampsia. Experimental design: Maternal serum levels of calcyclin and heat shock protein 90 are compared throughout pregnancy from the first trimester till term among women with preeclampsia (n = 43) and age-matched normotensive pregnant controls (n = 46). A serum-based 2D LC-MS assay using Parallel Reaction Monitoring is applied to quantify both calcyclin and heat shock protein 90. Results: Serum levels of calcyclin are significantly lower in patients with preeclampsia in the second trimester of pregnancy as compared to controls (p < 0.05). Serum levels of heat shock protein 90 are significantly higher in patients with preeclampsia in the third trimester as compared to controls (p < 0.001). Conclusion and clinical relevance: Both interacting proteins calcyclin and heat shock protein 90 are notably changed in preeclamptic patients compared to controls. Calcyclin is already decreased before the onset of preeclampsia in the second trimester and HSP90 is strongly increased in the third trimester. This suggests that these proteins may play a role in the pathogenesis of preeclampsia and ought to be investigated in large cohort studies as molecular biomarkers

Periostin Is Expressed by Pericytes and Is Crucial for Angiogenesis in Glioma

The expression of the matricellular protein periostin has been associated with glioma progression. In previous work we found an association of periostin with glioma angiogenesis. Here, we screen gliomas for POSTN expression and identify the cells that express periostin in human gliomas. In addition, we study the role of periostin in an in vitro model for angiogenesis. The expression of periostin was investigated by RT-PCR and by immunohistochemistry. In addition, we used double labeling and in situ RNA techniques to identify the expre

Chemokine receptor CCR7 expression predicts poor outcome in uveal melanoma and relates to liver metastasis whereas expression of CXCR4 is not of clinical re

Purpose. To examine the prognostic relevance of expression of the chemokine receptors CCR7 and CXCR4 and its ligand CXCL12 in uveal melanoma in nonmetastatic and metastatic patients with correlation to liver metastasis and overall survival. Methods. Primary uveal melanoma specimens from 19 patients with correlating liver metastasis specimens and 30 primary uveal melanoma specimens of patients without metastasis were collected between the years 1988 and 2008. Expression of CCR7, CXCR4, and CXCL12 were studied using immunohistochemistry. Single nucleotide polymorphism (SNP) arrays were used to examine gains or losses of chromosomes 1, 3, 6, and 8 and the regions of CCR7 (17q12-q21.2), CXCR4 (2q21), and CXCL12 (10q11.1) genes. Results. Strong cytoplasmic staining for CCR7 correlated with the presence of epithelioid cells (P = 0.037), tumor thickness (P = 0.011), lymphocytic infiltration (P = 0.041), and necrosis (P = 0.045). Nuclear staining for CXCR4 correlated with lymphocytic infiltration (P = 0.017). CXCL12 showed no correlation to histologic parameters. Single nucleotide polymorphism analyses showed no copy number variations in the regions of CCR7, CXCR4, or CXCL12. Strong expression of CCR7 was observed in 76% of the metastatic patients and 0% of nonmetastasis patients. In multivariate analysis, CCR7 staining was inversely correlated to overall survival and disease-free survival, whereas CXCR4 nuclear staining was not. Conclusions. Our data suggest that CCR7 plays a role in uveal melanoma metastasis and is associated with poor survival. CCR7 and its involved related pathways are of prognostic value in uveal melanoma and may prove to be a target for therapeutic intervention

Serum mir-373-3p and mir-194-5p are associated with early tumor progression during folfirinox treatment in pancreatic cancer patients

In this study, we explored the predictive value of serum microRNA (miRNA) expression for early tumor progression during FOLFIRINOX chemotherapy and its association with overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC). A total of 132 PDAC patients of all disease stages were included in this study, of whom 25% showed progressive disease during FOLFIRINOX according to the RECIST criteria. MiRNA expression was analyzed in serum collected before the start and after one cycle of chemotherapy. In the discovery cohort (n = 12), a 352-miRNA RT-qPCR panel was used. In the validation cohorts (total n = 120), miRNA expression was detected using individual RT-qPCR miRNA primers. Before the start of FOLFIRINOX, serum miR-373-3p expression was higher in patients with progressive disease compared to patients with disease control after FOLFIRINOX (Log2 fold difference (FD) 0.88, p = 0.006). MiR-194-5p expression after one cycle of FOLFIRINOX was lower in patients with progressive disease (Log2 FD −0.29, p = 0.044). Both miRNAs were predictors of early tumor progression in a multivariable model including disease stage and baseline CA19-9 level (miR-373-3p odds ratio (OR) 3.99, 95% CI 1.10–14.49; miR-194-5p OR 0.91, 95% CI 0.83–0.99). MiR-373-3p and miR-194-5p did not show an association with OS after adjustment for disease stage, baseline CA19-9, and chemotherapy response. In conclusion, high serum miR-373-3p before the start and low serum miR-194-5p after one cycle are associated with early tumor progression during FOLFIRINOX.</p